Method of preparing and using compositions extracted from vegetable matter for the treatment of cancer

ABSTRACT

A composition is prepared by extracting phytochemicals from plant matter. This composition is enriched preferably in isoflavones, lignans, saponins, catechins and phenolic acids. Soy is the preferred source of these chemicals: however, other plants may also be used, such as red clover, kudzu, flax, and cocoa. The composition is a dietary supplement for treatment of various cancers, pre- and post-menstrual syndromes, and various other disorders.

[0001] This is a formal application that replaces provisionalapplication Serial No. 60/060,549 filed Oct. 2, 1997.

[0002] This invention relates to compositions extracted from vegetablematter and more particularly to phytochemicals, including saponogeninsand saponins, catechins, lignans, phenolic acids, catechins andisoflavones, and especially those extracted from a family of plantsincluding soy, flax, tea, and cocoa and methods of using thesecompositions as nutritional supplements or food additives.

BACKGROUND

[0003] Plant materials are known to contain a number of classes oforganic low molecular weight compounds which exert bioactivity invarious animals. Historically, these compounds have been considered tobe somewhat non-nutritive, however, recent scientific evidence nowsuggests these compounds may play an important role in the maintenanceof health, in chemoprevention, and in the mitigation of certainconditions or diseases associated with the circulation of sex hormones,including sleep disorders and vaginal dryness.

[0004] Edible plants normally contained in the diet, or materials usedas herbal remedies/dietary supplements, may contain collections ofstructurally related compounds. These related substances are oftenunique in their amounts and distribution when compared among variousplant sources. The most notable groups of compounds exhibitingbioactivity are known as flavonoids, isoflavones, saponins, lignans,alkaloids, catechins and phenolic acids.

[0005] Epidemiology studies relating diet to disease suggest thatdietary components may predispose populations to reduced risk of certaindiseases. Far eastern populations consuming soy have reduced rates okbreast, prostate and colon cancers and coronary heart disease, whilepopulations in Finland have reduced rates of prostate cancer.Researchers are just now studying the specific compounds in the diet tounderstand the basis for the epidemiological observations.

[0006] Among the various plants consumed in the diet, several are richsources of phytochemicals. Soy products contain high amounts ofisoflavones and saponins. Unretined diet grains include plants such aswheat, psyllium, rice, flax and oats that contain lignans. Cocoacontains catechins and phenolic acids. Certain non-dietary plants arealso sources of the same chemical molecules, such as lignans andisoflavones in kudzu root or red clovers. Isoflavones and lignans act asweak estrogenic substances. Tea plants are also a rich source ofphytochemicals, including catechins and phenolic acids.

[0007] Isoflavones can be used alone to treat or prevent breast cancer,prostate cancer, skin cancer, and colon cancer or as mechanisminhibitors. Isoflavones alone may also reduce or prevent varioussymptoms related to the onset and duration of menopause, including hotflashes and osteoporosis. Isoflavones alone may also be effective incertain cardiovascular applications, including heart disease, reducingcholesterol-lipid levels, modulating angiogenesis, and other vasculareffects. Moreover, isoflavones alone have been implicated in reducingheadaches, dementia, inflammation, and alcohol abuse, as well asimmunomodulation.

[0008] Lignans alone have been implicated in preventing or treatingbreast cancer, prostate cancer and colon cancer as well as reducing hotflashes, preventing osteoporosis and showing antiviral potential.Lignans also have antimitotic and fungicidal activity, plant lignan, thecatecholic nordihydro-guaiaretic acid, was a potent antioxidant onceused by the food industry.

[0009] Saponins alone have been implicated in preventing or treatingskin cancer, colon cancer, reducing serum cholesterol, and inimmunomodulation and antiviral activity. Saponins also exhibitantioxidant effects and act as free radical scavengers.

[0010] Phenolic acids have shown antioxidant activity.

[0011] People who eat a high soy diet show reduction of many of theseabove-discussed symptoms. This suggests that ingesting a combination ofthese phytochemicals in a ratio such as that found in soy may result inan additive or synergistic effect. However, a high soy diet has someundesirable effects, including flatulence, undesirable taste, andhesitancy among Western consumers to change their lifestyle toincorporate soy in their diets, even for such benefits.

[0012] Isoflavones, which are heterocyclic phenols, are understood toinclude the soy compounds genistin, daidzin and glycitein, as well asbiochanin A, equol, formononetin, and o-desmethylangolensin and naturalderivatives thereof. These compounds and their aglycone or de-methylatedaglycone forms, such as genistein and daidzein, are believed to havesimilar activities once they are ingested. They are sometimes referredto as phyto-estrogens.

[0013] Lignans are defined to be compounds possessing a2,3-dibenzylbutane structure. They include matairesinol,secoisolariciresinol, lariciresinol, isolaniciresinol,nordihydroguaiaretic acid, pinoresinol, olivil, other compounds whichmay be precursors of enterolactone and enterodiol and modificationsthereof, including diglucosides.

[0014] Phenolic acids include p-hydrobenzoic acid, protocatechuic acid,and vanillic acid. Other phenolic acids are chlorogenic acid, caffeicacid, ferulic acid, gallic acid, sinapic acid, syringic acid, coumaricacid, cinnamic acid, gentisic acid, salicylic acid, hydroxy benzoic acidand hydroxy phenyl acetic acids and derivatives. This list of phenolicacids should be understood to include the various isomers andderivatives found in the natural vegetable source.

[0015] Catechins, or flavan-3-ols, include epigallocatechin, catechin,epicatechin and gallocatechin.

[0016] Saponogenins are C-27 sterols in which the side chain hasundergone metabolic changes to produce a spiroketal. Saponogenins occurnaturally as saponins, which are 3-O-glycosides of the parent steroid ortriterpenes. Digitonin from Digitalis is a saponin. Saponins includeglucosides of sapogenin such as triterpenoids or steroids andsaccharides such as glucose, arabinose, galactose or glucuronic acid.Typical examples of leguminous saponins are glycyrrhizin (glycyrrhetinicacid+glucuronic acid) contained in Glycyrrhiza glabra, soysaponincontained in soybean and alfalfasaponin contained in Medicago sativa.Saponins also include chemical entities identified as triterpene phenolssuch as tomatine, soyasapogenols A, B, C, D, E and F, ginsengosidefraction 3 and 4, medicagenic acid, hederagenin, glycyrrhizin digitonin,quillaja saponin, lucernic acid and zahnic acid. The naturalmodifications of these compounds found in the vegetable source are alsoincluded in this identification.

[0017] A need exists for an improved composition consistingsubstantially of isoflavones, lignans, saponogenins, saponins, and/orphenolic acids which will produce improved results over any of thesetaken alone. Furthermore, a need exists for a composition in which thebeneficial phytochemicals are enriched as compared to their originalsource. This permits individuals to conveniently consume suchphytochemicals as a nutritional supplement or as a food additive.

SUMMARY OF THE INVENTION

[0018] An object of this invention is to provide a convenient way forindividuals to consume isoflavones, lignans, saponins, catechins and/orphenolic acids, either as a nutritional supplement or as an ingredientin a more traditional type of food.

[0019] An other object of this invention is to provide an optimizedextract composition of phytochemicals which is in sufficientconcentration to be delivered in an easy to consume dosasge such as apill, tablet, capsule, liquid or ingredient in a food.

[0020] Yet another object of this invention is to prepare thephytochemical extract to be delivered as a topical application in acream or lotion. In this form, the isoflavones, lignans, saponins,catechins and/or phenolic acids are dispersed and suspended in asuitable liquid or gel matrix to render a stable cream or lotion as thedelivery vehicle.

[0021] A further object or this invention is to provide an extractconcentrate which is closely similar in chemical composition to thechemical entities found in the natural plant source.

[0022] In keeping with this aspect of the invention, the isoflavones,lignans, saponins, catechins and/or phenolic acids are extracted from asuitable vegetable source to render a composition which is substantiallymore concentrated than the original material and by more than 5 times inone or more of the desired bioactive components.

[0023] This extract may be used alone or combined with one or more otherplant extracts to produce the optimized composition. Further, thisextract composition may be formulated with one or more other dietarynutrients, such as vitamins, minerals, amino acids, etc., to provide anutritional supplement further optimized for a desired health effect.All these ingredients may be combined with necessary binders,excipients, preservatives, colors and the like known to those in theindustry in order to produce a suitable tablet, capsule, pill, liquid,cream, powder or food ingredient.

[0024] These phytochemicals may be packaged and provided in final formby means known to the supplements and food ingredient industries. Thematerials are intended to provide health and well-being benefits.

DETAILED DESCRIPTION OF THE INVENTION

[0025] The improved composition is obtained by fractionating a plantsource high in isoflavones, lignans and other phytochemicals such asdefatted soybean flakes, soy molasses, soy whey, red clover, alfalfa,flax, cocoa, tea, or kudzu root. These may be fractionated along or incombination with these other plants known to be high in the variousisoflavones, lignans, saponins, catechins and phenolic acids. Thefractionation results in substantially removing water, carbohydrates,proteins, and lipids from the source material. The fractionation methodmay be preferably that disclosed in co-pending U.S. Pat. No. 5,702,752or U.S. Pat. No. 4,428,876, or an extraction using ethyl acetate orn-butanol may be used. U.S. Pat. No. 5,702,752 is assigned to theassignee of this invention.

[0026] Other extraction processes, which may be used alone or incombination, include differential solubility, distillation, solventextraction, adsorptive means, differential molecular filtration andprecipitation.

[0027] The preferred composition is an improvement over known commercialmaterials regarding the amount of phytochemicals per gram of substanceand the amounts of different phytochemicals present which affectphysiologic function.

[0028] These natural substances have been consumed in food sources forlong periods of time and more closely relate to the substances consumedwhich provide the basis for the epidemiological evidence for healthbenefits. Additional benefits may be derived from improved physicalproperties relative to phytochemicals chemically modified from theiroriginal food source form.

[0029] The resulting composition is expected to comprise in a preferredform between 5% and 95% isoflavones, between 0% and 70% lignans, andbetween 2% and 70% saponins and sapogenins. In a more preferred form,the composition will be extracted from soy. In another preferred form,the composition will contain a ratio of (saponins plus saponogenins) toisoflavones from 1 100 to 100 1, with the isoflavones consistingpredominantly of naturally occurring derivatives of genistein and/or itsprecursor biochanin A and daidzein and/or its precursor formononetin,with a ratio of the genistein derivatives to daidzein derivatives from100 1 to 1 100. Preferably, the isoflavones are predominantlyglycosylated derivatives.

[0030] The composition's ratios may be readily varied by changing theplant source or by combining several plant sources for extraction. Thus,as further study shows which phytochemical combinations are moreefficacious for certain health effects, the particular composition willalso vary.

[0031] It is known that isoflavones, lignans, and saponins can be usedadvantageously to treat or prevent various cancers, including breastcancer, prostate cancer, skin cancer, and colon cancer.

[0032] It is believed that the improved composition will provideincreased benefits in the form of chemoprevention. Recent experimentsappear to confirm this belief.

EXAMPLE 1

[0033] An initial series of animal studies was made to investigate theeffects of dietary soy products on the growth of s.c. (SUBCUTANEOUS)implanted LNCaP in male SCID mice. A high isoflavone-containing soyprotein isolate (SPI) (2.0 mg isoflavones/g SPI) is provided by ProteinTechnology International (St Louis, Mo.) A soy phytochemicals extract,soy phytochemicals concentrate (SPC) which contains 28.5% total soyisoflavones and a diverse amount of other soy phytochemicals, isprovided by Archer Daniels Midland Company (Decatur, Ill.). Thesematerials were used to prepare six experimental diets Table 1 showsingredients of the diets.

[0034] Eight-week-old male SCID mice were s.c. injected on the rightflank with 2×10⁶ LNCaP cells from hosts, randomized into six groups(n=10) and assigned to one of the experimental diets. Food intake, bodyweight, and tumor volume were measured. At the termination of theexperiment, blood samples were collected and serum separated for PSAanalysis. An aliquot of tumor tissues was formalin-fixed,paraffin-embedded, and cut into 4 μm sections for in situ histochemicaldetection of apoptotic cells, and immunohistochemical analyses ofangiogenesis and proliferation. Another aliquot was prepared for celllysates for western blot to determine the expression ofapoptosis-related gene products.

[0035] Table 2 summaries the effects of treatment on food intake, bodyweight, isoflavone intake and tumor volume. Soy products did notsignificantly alter food intake or body weight. Compared to casein-fedcontrols, tumor volumes from mice treated with SPI (20%), SPC (1.0), andSPI and SPC (1.0%) were reduced by 12%, 28% (P<0.04), or 40% (P<0.005),respectively. Factorial analysis indicated that there was no significanteffect of protein source on tumor growth. Linear regression analysisindicated that tumor volumes were inversely correlated to total dietaryisoflavones (Tumor volume (cm³)=−0.0008+2.121×Isoflavones (mg), R²=0.76,p<0.03).

[0036] Table 3 shows the effects of SPC at 1.0% of the diet onapoptosis, proliferation, and angiogenesis of tumors from a pilot study.It indicates that dietary supplementation of soy phytochemicals inhibitsthe growth of LNCaP tumor in vivo by enhancing apoptosis and inhibitingproliferation of tumor cells. Its inhibitory effect on tumorangiogenesis is not significant which may be due to small sample size(n=2).

[0037] Results from in vitro study showed that genistein and soyphytochemical concentrate inhibited secretion of PSA by LNCaP cells intomedia PSA concentrations were reduced 68% and 70% by 25 and 50 uM ofgenistein treatment respectively, and 31% and 42% by 25 and 50 uM of soyphytochemical concentrate treatment respectively. TABLE 1 Ingredients ofexperimental diets (grams) Diet 1 Diet 2 Diet 3 Diet 4 Diet 5 Diet 6casein SPI Casein/LSPC SPI/LSPC Casein/HSPC SPI/HSP SPI 0 200 0 200 0200 Casein 200 0 200 0 200 0 DL-methionine 3 3 3 3 3 3 Corn starch 150150 150 150 150 150 Sucrose 500 500 500 500 500 500 Cellulose, BW200 5050 50 50 50 50 Corn oil 50 50 50 50 50 50 Mineral Mix. S10001¹ 35 35 3535 35 35 Vitamin Mix. V10001¹ 10 10 10 10 10 10 Choline Bitartrate 2 2 22 2 2 Soy phytochemicals 0 0 2 2 10 10 Total (g) 1000 1000 1002 10021010 010 (isoflavones, mg/kg diet) 0 245 341 586 705 950

[0038] TABLE 2 Final bouy weight, total food intake, total isoflavoneintake, and tumor volume Food intake Tumor volume Treatment Body weightgrams/m Total isoflavone (cm³) Casein 22.4 ± 0 5¹ 46 6 ± 3 1  0.00 ± 000 2.32 ± 0.31² SPI 23.1 ± 0 7 46.2 ± 2.8 17 00 ± 6.37 2.06 ± 0 32Casein/LSPC 12.4 ± 0.7 41 2 ± 3.4 14 03 ± 14 1.88 ± 0.35 SPI/LSPC 22.6 ±0.6 50 1 ± 4.7 29 36 ± 2.76 11.66 ± 0.29* Casein/HSPC 22.2 ± 0.7 44 8 ±6.1 76.38 ± 10.40 1.64 ± 0.22* SPI/HSPC 22.0 ± 0.6 47 5 ± 1.7 92.53 ±3.22 1.39 ± 0.30**

[0039] TABLE 3 Effects of treatment on apoptotic index (AI, % TUNEL),proliferation index (PI, % PCNA Staining) and angiogenesis (microvesseldensity) Treatment AI (% TUNEL) PI (% PCNA) Microvessel Density Control(n = 2) 6 07 ± 0.88 60 1 ± 1.1 12.5 ± 3.8 Casein/HSPC (n = 2) 10 75 ± 054 51 7 ± 1 3 9 7 ± 0.7 P value <0 02 <0 01 >0 05

[0040] In summary, preliminary results indicate that soy productsinhibit the s.c. growth of LNCaP tumor in SCID mice, possibly viainduction of apoptosis, and inhibition of angiogenesis andproliferation.

[0041] Isoflavones or lignans can alleviate menopausal-related symptomssuch as hot flashes and osteoporosis as well as alleviate symptomsassociated with menstruation. This is further believed to be due totheir estrogenic activity. It is believed that the improved compositiondescribed here will alleviate these symptoms even more effectively.

[0042] Also, isoflavones positively affect variouscardiovascular-related conditions, including heart disease, cholesterol(saponins also positively affect cholesterol), angiogenesis and othervascular effects. It is believed that the improved composition willproduce results for these cardiovascular conditions at least asbeneficial as those hitherto known and at a reduced cost.

[0043] As explained earlier, isoflavones, lignans, and saponins areknown to individually positively affect various neurological andimmunological symptoms. It is believed that the improved compositionwill result in alleviating neurological and immunological symptoms atleast as well as those compounds hitherto known and at a reduced cost.Moreover, it would be expected that some synergism would arise out ofthe combination described herein.

[0044] The improved composition may be administered orally,parenterally, for instance, subcutaneously, intravenously,intramuscularly, intraperitoneally, by intranasal instillation or byapplication of an aerosol spray to mucous membranes, or to the skin byan ointment or a cream.

[0045] Administering the improved composition may be done with anysuitable carrier, in solid or liquid dosage form such as tablets,capsules, powders, soft gels, solutions, suspensions, emulsions,ointments, or creams. The improved composition may also be administeredas a food supplement or as a food ingredient.

[0046] The amount of the improved composition administered will varydepending on the person, the mode of administration, and the desiredresult. An effective amount is expected to be 10 mg to 2000 mg/per dose.

EXAMPLE 2 Tablet Manufacture

[0047] The composition provided for in this patent may be used toprepare tablets or other dosage forms. An example of a capsulepreparation is provided in Example 2. The hither the concentration ofthe active component, the easier it is to form a tablet or emulsion.This leads to an added ability to incorporate other dietary nutrients.An example would be to prepare a phytochemical tablet which incorporatescalcium and vitamin E as a supplement to maintain bone health and/orreduce post menopausal symptoms such as hot flashes. In an example ofthis embodiment, a 600 mg dry compression tablet was prepared containinga total of 125 mg of isoflavones concentrate (50 mg isoflavonecompound). Included in the tablet formulation was a source of calciumand magnesium.

[0048] Dry compression tablets were produced by first blending thefollowing ingredients: 4 kg of the improved composition (39.83%isoflavones), 1.91 kg sorbitol, 0.095 kg magnesium stearate, and 13.11kg dicalcium phosphate in a 120 quart capacity Hobart mixer. This blendof ingredients was then dry compressed at 1 ton pressure with a StokesBB2 simple press into tablets having a total weight of 600 mg containing125.53 mg of the improved composition and therefore 50 mg of totalisoflavones.

[0049] Alternatively, a photochemical concentrate may be provided in asingle dosage form, a skin cream or as a food ingredient added toconventional food in amounts from 10 mg to 2000 mg/per dose, the purposeof which is to exert a positive effect on health and well being. Thesebenefits include: cancer prevention, estrogen and sex hormone relatedmaladies, inhibition of the pituitary-thyroid-gonadotrophic axis,alcohol dependency reduction, modulation of the cardiovascular, immuneand nervous systems, antiviral effects and analgesic effects.

EXAMPLE 3

[0050] Two-piece gelatin capsules were produced by filling the receivingend of the empty size “0” capsules with 0.106 g of the improvedcomposition (44.35% isoflavones) and closed with the capping end,providing a capsule containing 47.2 mg of total isoflavones.

EXAMPLE 4

[0051] A comparison between various sources of phytochemicalpreparations is given in Table 4. It is readily seen that thephytochemical components of the composition of the “IsoflavoneConcentrate” of this invention is substantially higher than thecorresponding amounts in the natural vegetable materials. Notably, theamount of glycone isoflavones and saponins are over 100 times moreconcentrated compared to the food source and over twenty times moreconcentrated compared to the germ of the plant which naturallyconcentrates these phytochemicals. Comparison of the “IsoflavoneConcentrate” of this invention to other concentrates shows that theisoflavone fraction predominates in these latter products, reducing theamount of other healthful phytochemicals. Additionally, the extractionmethods of these other products employ techniques which modify thecomponents, particularly the isoflavones, so that they are not identicalto the substances found in the natural vegetable material (U.S. Pat. No.5,637,562).

[0052] One version of the improved composition was compared to otherpreviously described compositions. The results are shown in Table 4.TABLE 4 Comparative Products to the Invention Isoflavone IsoflavoneGlycosides in Aglycones in Genistein/ Phenolic Product Product ProductDaidzein Lignans Saponins Acids Example (mg/g) (mg/g) Ratio (mg/g)(mg/g) (mg/g) Improved 401.0  3.37  1.06 to 1 0.2 460.7 25.47composition Soybean 1.748-2.776^(a) 0.044^(a)-0.075  1.59-2.7 NA 0.9-3.2^(b) Soy Flour  1.969^(a)  0.045^(a)  3.58 0.0013  2.870^(c)(defatted Soy germ  24.32^(d)  0.85^(d) NA 16.7-1.98^(b) NA Product^(c)NA   2.5-6.5^(c)  0.5-3.5 NA NA NA patent (PTI) Product^(i) NA  5.1-14.7^(i) 0.433-3.48 NA NA NA patent (PTI) Product^(g) NA  1.7-3.5^(g)  0.66-2.86 NA NA NA patent (PTI) PTI NA 970 12.8 NA NA NAproduct^(h) PTI NA 640  2.0 NA NA NA product^(h) Soy Molasses  27.6  0.1 1.37 NA NA  5.788 (dried) Novogen^(i)  0.0 550 1-1.7 to 1 NA NA NA

EXAMPLE 5

[0053] The improved composition, containing the glycoside forms ofisoflavones, has as one aspect an improved solubility at bodytemperature over the previously described compositions containing theaglycoside forms.

[0054] Separate solutions (0.02% in distilled water) were made forgenistein, genistin, daidzein, daidzin, and isoflavone concentrate involumetric flasks. Samples were then placed in a 37° C. water bath for17 hours, followed by rapid filtration through a 0.2 micron syringe-typefilter to remove particulates. Filtered samples were then analyzed forisoflavone concentration by HPLC. Results are tabulated as shown inTable 5. TABLE 5 Differential Solubility of Isoflavone Glvcosides vs.Aglycones Isoflavone sample Genistein (ppm) Genistin (ppm) Daidzein(ppm) Daidzin (ppm) Genistein 7 42 Genistin 33.89 Daidzein 3 64 Daidzin48 51 Isoflavone 0 492 30 075 0.672 37 69 Concentrate

[0055] The glycoside forms, genistin and daidzin, are at least 4.57 and13.32 fold higher in concentration at 37° C. than their correspondingaglycone forms, respectively.

[0056] The modifications made to the isoflavones are to remove thecarbohydrate attached to the isoflavone moiety. This modificationrenders the isoflavone less soluble in water. Maintenance of the naturalmodification, glycosylation, enhances solubility. This fact is shown inthe comparative solubility chart of Table 5. This chart shows that thegenistin isoflavone is 4.6 times higher and the daidzin isoflavone is13.3 times higher than the corresponding non-glycosylated form. Highersolubility can lead to better bioavailability to intestinal organisms.The glycosylation does not inhibit absorption in the gut because theintestinal microflora convert the glycone form to the aglycone formbefore absorption occurs.

EXAMPLE 6 Extraction of Lignans from Flax

[0057] Lignans can be readily extracted from flax using this followingmethod.

[0058] 978 g of defatted flax meal (F1) was extracted with 2000 g of 85%ethanol at 40° C. for 10 minutes, forming a slurry. The resulting slurrywas filtered and extraction was repeated twice with a total of 6000 g ofethanol.

[0059] The ethanolic fraction was then evaporated under vacuum at 70°C., resulting in an aqueous fraction of 1186 g. The aqueous fraction wascombined with 1000 g of water and mixed.

[0060] The mixed sample was then ultra-filtered through a 5000 molecularweight cutoff membrane, resulting in a 767 g permeate fraction and aretentate action of 1283 g.

[0061] The retentate fraction %vas freeze-dried, resulting in a 27.84 gsample (F2).

[0062] The 767 g permeate fraction at 50° C. was fed to a 35 ml bedvolume, XAD-4 resin column at a rate of 10 ml/min. The column effluentwas collected and dried, resulting in a 14.8 g sample (F3). XAD-4 is atrademark for an absorbent resin, available from Rohm & Haas.

[0063] The column was then eluted with four bed volumes (140 ml) of 70%ethanol at 50° C. The eluent sample was evaporated under vacuum at 70°C. and dried, resulting in a 1.79 g sample (F4). The four fractions werethen analyzed for their lignan content, measured as the concentration byweight of secoisolariciresinol. As Table 6 shows, this extraction methodenriches lignan concentration. TABLE 6 LIGNAN CONCENTRATIONS ASSECOISOLARICIRESINOL FRACTION F1 F2 F3 F4 SECO. CONG. (mg/g) 2.3 1.9 4.813.4 PHENOLIC ACID

[0064] While the present invention has been disclosed in terms of thepreferred embodiment in order to facilitate a better understanding ofthe invention, it should be appreciated that the invention can beembodied in various ways without departing from the principles of theinvention. Therefore, the invention should be understood to include allpossible embodiments, modifications, and equivalents to the describedembodiment which do not depart form the principles of the inventions asset out in the appended claims.

1. A composition from a plant matter in which the composition isenriched in at least two of the phytochemicals selected from the groupconsisting of isoflavones, lignans, saponins, catechins and phenolicacids.
 2. The composition of claim 1 which essentially consists of atleast 70% by weight phytochemicals selected from the group comprisingisoflavones, lignans, saponins, catechins and phenolic acids.
 3. Thecomposition of claim 1 in which at least one of the selectedphytochemicals comprises at least 10% by weight of the composition. 4.The composition of claim 1 which essentially consists of at least 80% byweight phytochemicals selected from the group comprising isoflavones,lignans, saponins, catechins and phenolic acids.
 5. The composition ofclaim 1 which essentially consists of at least 90% by weightphytochemicals selected from the group comprising isoflavones, lignans,saponins, catechins and phenolic acids.
 6. The composition of claim 1 inwhich the ratio of isoflavones to lignans is selected from the range ofabout 1000.1 to about 1.50.
 7. The composition of claim 1 in which theratio of isoflavones to saponins is selected from the range of about1.10 to about 10.1.
 8. The composition of claim 1 in which the ratio orisoflavones to phenolic acids is selected from the range of about 100 to1 to about 1 to
 100. 9. The composition of claim 1 in which the ratio oflignans to saponins is selected from the range of out 100 to 1 to about1 to
 100. 10. The composition of claim 1 in which the ration of lignansto phenolic acids is selected from the range of about 100 to 1 to about1 to
 100. 11. The composition of claim 1 in which the ratio of saponinsto phenolic acids is selected from the range of about 100 to 1 to about1 to
 100. 12. The composition of claim 1 in which the ratio of catechinsto phenolic acid is selected form a range of about 100 to 1 to about 1to
 100. 13. The composition of claim 1 in which the isoflavones arepresent in an amount from approximately 5% to approximately 90% byweight.
 14. The composition of claim 1 in which the lignans are presentin an amount from about 1% to about 70% by weight.
 15. The compositionof claim 1 in which the saponins are present in an amount from about 5%to about 70% by weight.
 16. The composition of claim 1 in which thephenoiic acids are present in an amount from about 1% to about 70% byweight.
 17. The composition of claim 1 in which the isoflavones areselected from the group consisting essentially of genistein, daidzein,glycitein, biochanin A, formononetin, and natural modifications thereof.18. The composition of claim 1 in which the lignans are selected fromthe group consisting essentially of matairesinol, secoisolariciresinol,lariciresinol, isolariciresinol, nordihydroguaiaretic acid, pinoresionl,olivil, and precursors of enterolactone and enterodiol and naturalmodifications thereof.
 19. The composition of claim 1 in which thesaponins are selected from the group consisting essentially of tomatine,soyasapogenols A, B, C, D, E and F, soysapnin, alfalfasaponin,ginsengoside fraction 3 and 4, medicagenic acid, hederagenin,glycyrrhizin digitoning, quillaja saponin, lucernic acid, zahnic acid,and natural modifications of these compounds.
 20. The composition ofclaim 1 in which the phenolic acids are selected from the groupconsisting essentially of chlorogenic acid, caffeic acid, ferulic acid,gallic acid, sinapic acid, syringic acid, vanillic acid, coumeric acid,cinnamic acid, gentisic acid, salicylic acid, hydroxy benzoic acid andhydroxy phenyl acetic acids and derivatives thereof.
 21. The compositionof claim 1 in which catechins are selected from the group consistingessentially of catechin, epicatechin, gallocatechin, andepigallocatechin.
 22. The composition of claim 1 in which the plantmatter is selected from one or more of the group consisting essentiallyof soy, red clover, kudzu, flax, alfalfa, tea, and cocoa.
 23. Thecomposition of claim 1 in which the plant matter is soy.
 24. Thecomposition of claim 23, in which the soy is selected from the groupconsisting of soybean, soy foods, soy molasses, soy whey, soy protein,and soy flour.
 25. A product for oral delivers comprising a compositionextracted from plant matter which is enriched in two or more of thephytochemicals selected from the group consisting of isoflavones,lignans, saponins, catechins and phenolic acids.
 26. The product ofclaim 25 wherein the product is selected from the group consisting oftablets, capsules, pills, concentrates, powders, liquids, and added foodingredients.
 27. The product of claim 26 comprising tablets comprisinga. the plant matter composition; and b. a filler selected from the groupconsisting of sorbitol, lactose, cellulose and dicalcium phosphate. 28.The product of claim 27 additionally comprising a dietary supplementalnutrient selected from the group consisting of dicalcium phosphate,magnesium stearate, calcium citrate, calcium malate, other calciumsources, vitamins and minerals.
 29. The oral delivery product of claim27 wherein the product comprises between about 15% and about 25% byweight of the composition and between about 65% and about 85% by weightof the filler.
 30. The product of claim 25 wherein the product comprisesa. between about 15% and about 25% by weight of the composition, b.between about 60% and about 84% by weight of the filler; and c. betweenabout 1% and about 25% by weight of the dietary supplemental nutrient.31. The oral delivery product of claim 26 comprising capsules includinga. a predetermined dosage of the plant matter composition; and b. agelatin capsule.
 32. The oral delivery product of claim 26 wherein theplant matter composition is extracted from plants selected from thegroup consisting of soy, red clover, kudzu, flax, alfalfa, tea, andcocoa.
 33. The oral delivery product of claim 23 wherein the productcomprises between about 10 milligrams and about 2000 milligrams of theplant matter composition.
 34. A method of treating a disease selectedfrom the group consisting of breast cancer, skin cancer, and coloncancer, said method comprising the step of administering to the subjecta therapeutically effective amount of a composition extracted from plantmatter which is enriched in at least one of the phytochemicals selectedfrom the group of isoflavones, lignans, saponins, catechins and phenolicacids.
 35. The method of claim 34 wherein the treatment is for breastcancer.
 36. The method of claim 34 wherein the treatment is for skincancer.
 37. The method of claim 34 wherein the treatment is for coloncancer.
 38. A method of treating at least one disease selected from thegroup consisting of urinary cancer, bladder cancer, and prostate cancerin a subject, said method comprising the step of administering to thesubject a therapeutically effective amount of a composition extractedfrom plant matter which is enriched in at least one of thephytochemicals selected from the group of isoflavones, lignans,saponins, catechins and phenolic acids.
 39. The method of claim 38wherein the treatment is for urinary cancer.
 40. The method of claim 38wherein the treatment is for bladder cancer.
 41. The method of claim 38wherein the treatment is for prostate cancer.
 42. A method of treatingone disorder selected from the group consisting of migraine headache anddementia in a subject, said method comprising the step of administeringto the subject a therapeutically effective amount of a compositionextracted from plant matter which is enriched in at least one of thephytochemicals selected from the group of isoflavones, lignans,saponins, catechins and phenolic acids.
 43. The method of claim 42wherein the treatment is for migraine headache.
 44. The method of claim42 wherein the treatment is for dementia.
 45. A method of reducingalcohol dependency in a subject said method comprising the step ofadministering to the subject a therapeutically effective amount of acomposition extracted from plant matter which is enriched in at leastone of the phytochemicals selected from the group of isoflavones,lignans, saponins, catechins and phenolic acids.
 46. A method ofreducing bloodstream cholesterol, reducing the risk of coronary heartdisease, or modulating blood lipid profiles in a subject, said methodcomprising the step of administering to the subject a therapeuticallyeffective amount of a composition extracted from plant matter which isenriched in at least one of the phytochemicals selected from the groupof isoflavones, lignans, saponins, catechins, and phenolic acids. 47.The method of claim 46 wherein bloodstream cholesterol is reduced. 48.The method of claim 46 wherein the risk of coronary heart disease isreduced.
 49. The method of claim 46 wherein blood lipid profiles aremodulated.
 50. A method of reducing or preventing hot flashes,osteoporosis, sleep disorders, vaginal dryness or premenstrual syndromein a subject, said method comprising the step of administering to thesubject a therapeutically effective amount of a composition extractedfrom plant matter which is enriched in at least one of thephytochemicals selected from the group of isoflavones, lignans,saponins, catechins, and phenolic acids.
 51. The method of claim 50wherein hot flashes are treated or prevented.
 52. The method of claim 51wherein osteoporosis is treated or prevented.
 53. The method of claim 51wherein premenstrual syndrome is treated or prevented.
 54. The method ofclaim 51 wherein sleep disorders is treated or prevented.
 55. The methodof claim 51 wherein vaginal dryness is treated or prevented.
 56. Thecomposition of claim 1 in which the plant matter is flax.
 57. Thecomposition of claim 56 which consists of at least about 1% by weightlignans.
 58. The composition of claim 56 which consists of at leastabout 50% by weight lignans.
 59. The composition of claim 1 in which theselected phytochemicals are in a substantially native form.
 60. Thecomposition of claim 1 in which the isoflavones are in a substantiallyglycosylated form.
 61. The composition of claim 1 which is added as asupplement to a food.
 62. The composition of claim 1 which is consumedas a dietary supplement.
 63. The composition of claim 1 in which theplant matter is tea.
 64. The composition of claim 1 in which the plantmatter is cocoa.
 65. A composition made by the process comprising thesteps of: a. extracting a defatted material from a group of vegetablematter consisting of protein, meal, whey, molasses, solubles and germsin a solution including an alcoholic solvent to produce a slurry; b.filtering the slurry of step (a) to produce an alcoholic fraction; c.evaporating said alcoholic fraction of step (b) to produce an aqueousfraction; d. ultrafiltering said aqueous fraction of step (c), e.feeding a permeate of step (d) through a resin column; and f. collectingan effluent from said column after said wash.
 66. The composition ofclaim 65 and the further step of preparing said effluent of step (f)into a form which is suitable for administering orally, said form beingtaken from a group consisting of a concentrate, dried powder, capsule,pellet, and pill.
 67. The composition of claim 66 wherein said driedpowder is a bulk volume of material for further manufacture to provideindividual dose sizes for said oral administration.
 68. The compositionof claim 65 wherein said vegetable matter is selected from a groupconsisting of soy, red clover, kudzu, flax, alfalfa, tea, and cocoa. 69.The composition of claim 65 wherein said vegetable matter is soy. 70.The composition of claim 65 wherein step (c) includes a step of dilutingsaid aqueous fraction.
 71. The composition of claim 65 and the addedstep of fractionating said effluent to select at least one of the groupconsisting essentially of isoflavones, lignans, saponins, catechins, andphenolic acid.
 72. The composition of claim 65 and the added step offractionating said effluent to select isoflavones.
 73. The compositionof claim 65 wherein the solution of step (a) is about 70% ethanol andthe extraction is carried out at about 40° C.
 74. The composition ofclaim 65 where the evaporation of step (c) is carried out under vacuumat about 70° C.